If only there was an allele that LESSENED the apprehensive and uncomfortable feelings I get when meeting new people.

As such negative feelings are the work of my amygdala, I’m wishing for some sort of LOSS-OF-FUNCTION allele that REDUCES the activity of neural circuits involved in the emotional processing of fear … but leaves other neural circuits untouched.

I just want something that takes the edge off new social experiences … yunno?

How about rs33977775 ? It contains a derived (as opposed to ancestral) T-allele that causes a Y135F change that disrupts the binding sites of the NPBWR1 receptor to its neuropeptide ligands (ie. LOSS-OF-FUNCTION). Amazingly, this receptor has a restricted pattern of gene expression only among limbic circuits involved in emotion and reward processing (ie. EXPRESSED IN EMOTION PROCESSING CIRCUITS ONLY).

In their report, a team of authors measured the reactions of 126 university students to various social stimuli and report that individuals who carry one of these loss-of-function T-alleles (about 30% of the population) show a more positive response to social interactions.

“… the AT group perceived facial expressions more pleasantly than did the AA group, regardless of the category of facial expression. Statistical analysis … also showed that the AT group tended to feel less submissive to an angry face than did the AA group.”

So it seems that rs33977775 may dial down the amygdala response to social stimuli … just enough to ace the job interview, but not so much that you inappropriately hug your new boss. Nice!

Unfortunately, this SNP is not covered by 23andMe v3 and there is no report yet on linkage disequilibrium via 1000 genomes. Since the frequency of the T-allele is low in African populations (1%) and about 10%-ish in other non-African populations, I guess the odds are that I’m an AA or AT.

What hurts more – a broken toe or a broken heart? Ask a parent and their forlorn 15 year-old who was not invited to the party that everyone is going to, and you might get different answers. In some cases, the internal anguish of social exclusion or estrangement, may even – paradoxically – be relieved by self-infliction of physical pain, which is construed by some neuro-psychiatrists as a coping mechanism, wherein endogenousopioids are released by the physical injury (cutting, for instance) and may then soothe the internal feeling of anguish.

While there are many social, and psychological factors pertaining to the way in which people cope with internal and external pain, a recent research article from Dr. Naomi Eisenberger’s lab sheds light on a very basic aspect of this complex process – that is – the similarities and differences of neural mechanisms underlying social and physical pain. In their recent paper, “Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection” [doi:10.1073/pnas.0812612106] the authors asked healthy participants to lay in an MRI scanner and play a video game of catch / toss the ball with other “real people” by way of a computer interface. During the game, the participant was rudely socially excluded by the other two players in order to induce the feelings of social rejection. Participants also completed an instrument known as the “Mehrabian Sensitivity to Rejection Scale” and were genotyped for an A-to-G SNP (rs1799971) located in the opioid receptor (OPRM1) gene. Previous research as found that the G-allele of OPRM1 is less expressed and that individuals who carry the GG form tend to need higher doses of opioids to feel relief from physical pain, and GG rhesus monkeys (interestingly, we share the same ancient A-to-G polymorphism with our primate ancestors) demonstrate more distress when separated from their mothers.

The results of the study show that the participants who carry the AA genotype are somewhat less sensitive to social rejection and also show less brain activity in the anterior cingulate cortex (an area whose activity has long been associated with responses to physical pain) as well as the anterior insula (an area often times associated with unpleasant gut feelings) when excluded during the ball-toss game. Further statistical analyses showed that the activity in the cingulate cortex was a mediator of the genetic association with rejection sensitivity – suggesting that the genetic difference exerts its effect by way of its role in the anterior cingulate cortex. Hence, they have localized where in the brain, this particular genetic variant exerts its effect. Very cool indeed!!

Stepping back, I can’t help but think of the difficulties people have in coping with internal anguish, which – if not understood by their peers – can, mercilessly, lead to further exclusion, estrangement and stigmatization. Studies like this one reveal – from behavior, to brain, to genome – the basic biology of this important aspect of our social lives, and can help to reverse the marginalization of people coping with internal anguish.

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The picture is of William Faulkner who is quoted, “Given the choice between the experience of pain and nothing, I would choose pain.” I wonder if he was an AA or a G-carrier? I feel rather lucky to find that my 23andMe profile shows an AA at this site.